Pathogenesis of Parasitic Infections

Question 1

What are the different kinds of leishmaniasis?

Answer 1

Visceral leishmaniasis

• Asia: Leishmania donovani
• Middle East/Africa/Asia: L. infantum variants
• Latin America: L. chagasi

Cutaneous leishmaniasis

• Old World: Mediterranean/Middle East: L. Infantum/L. major/L. tropica
• New world: Central and South America: L. braziliensis/amazonensis/mexicana

Question 2

Describe leishamaniasis’ life cycle.

Answer 2

The disease is caused by the sand-fly. A sand-fly will bite you, and transfer you a promastigote; those invade immune cells such as macrophages.

Inside the macrophage, it forms nests of amastigotes. The cells then burst, releasing lots of the pathogen to infect other cells.

Question 3

Describe the different clinical forms of cutaneous leishmaniasis.

Answer 3

Leishmania tropica:
A few weeks after being bitten, you’d get a papule on you body. Gradually, the papule would spread and become a lesion. The centre then becomes necrotic, and you get an ulcer formation.

Leishmania recidivans:
Some lesions can reactivate months or years later.

Sporotrichoid leishmania:
Some lesions can go along the lymphatic vessels.

Diffuse cutaneous leishmaniasis:
Some people are unable to generate an adequate response and so they get packed full of parasites.

Mucocutaneous leishmaniasis:
Some individuals get infected when they are younger, get a scar and years later, a portion of them will get a stuffy nose. It then becomes more marked and you start seeing these lesions around the area – the parasite can reactivate. It becomes a very destructive lesion.

Question 4

Describe the pathogenesis of cutaneous leishmaniasis.

Answer 4

ACUTE LESIONS:

• Tissue damage caused by inflammatory response to presence of parasites in macrophages
• Parasite killing by Th1 pro-inflammatory responses and macrophage killing.

LATENCY:
- Parasites remain present long-term. Regulatory immune response characterized by balance of Th1 and anti-inflammatory responses

RELAPSE (RARE):

• Alteration in immune response (i.e change in Th1 vs. immune regulation secondary to HIV, malnutrtition) may trigger relapse
• Mucocutaneous disease associated with strong but inadequate inflammatory response to parasites that have metastasized to mucosa
• Diffuse cutaneous leishmaniasis associated with uncontrolled parasite replication.
• Recividans – recurrence of lesions at old ulcer site.

Question 5

What are the three main species of schistosomiasis?

Answer 5

• Schistosoma mansoni: affects the hepatic and intestinal system
• S. haematobium: affects the urinary tract
• S. japonicum: affects the hepatic and intestinal system, just found in Asia

Question 6

As a recap, describe the schistosomiasis life cycle.

Answer 6

Water is contaminated with human faeces and the eggs are in the water
It develops into an intermediate stage called the miracidium, which infects the snail (amplifier).

They asexually reproduce in the snail, and release thousands of cercarie and this infects humans when they walk in contaminated water.
They develop into adults in the human (mesenteric system), undergo sexual reproduction and produce many eggs, which are then released into the environment again, continuing the life cycle.

Question 7

What is cercarial dermatitis?

Answer 7

It presents as a nasty allergic reaction when people who have becomes sensitised are exposed to cercarie in the water source.

Question 8

What is the key feature of the immune response to schistosomiasis?

Answer 8

The key feature of the immune response to schistosomiasis is the response to granuloma formation.

The eggs become organised into granulomas.
In schistosomiasis, you get these repeated episodes of inflammation, and then you get damage to the tissues, repair and fibrosis, which causes damage related to the disease.

This is a classical example of Th2-delayed hypersensitivity.

Question 9

How would you get hepato-intestinal schistosomiasis?

Answer 9

It occurs in infections with S.mansoni and S.japonicum. Again, the pathology is caused by the immune resposne to the egg.

Since the adults are in the mesenteric vessels, the female gives birth to many eggs and these go into the intestines, through the capillaries and are pushed by the immune response through the intestinal wall and through the mucosa and are excreted.

Question 10

Describe urinary schistosomiasis.

Answer 10

The adults live in the vessels around the bladder and they release eggs into these vessels – these are pushed through the mucosa in the bladder and pushed into the urine.

A symptom of urinary schistosomiasis is haematuria.
As a result of its prevalance in endemic areas, peeing blood has become so common that it is seen as a right of passage.

Because of inflammation to the bladder wall, you get damage to the bladder wall, which can lead to cancer development.

Question 11

Describe onchocerciasis.

Answer 11

It is a major blinding disease. It used to be a major cause of blindness in West Africa, but now there are effective control programme.

It is caused by the filarial parasite (Onchocerca volvulus), and it transmitted by blackflies (simulium).

It is distributed in equatorial regions of Africa, and Central and South America.

Question 12

Describe how you would get onchocerciasis from a blackfly.

Answer 12

A blackfly will bite you and transmit its larvae into you. The larvae migrates under the skin and develops into an adult (male and female).

After mating, the female releases thousands or larvae called microfilariae – these are taken up by the blackfly.

Question 13

Describe the pathology of onchocerciasis.

Answer 13

Repeated episodes of inflammation to presence of microfilariae leads to permanent damage and scarring in skin and eyes.

For an adult in an endemic area, you will be able to see the larvae in the dermis of the skin, but there won’t be an immune response. The parasite is actively down-regulating the host immune response.
It can switch off its downregulation if given treatment.

Question 14

Describe the clinical presentations of onchocerciasis.

Answer 14

Onchocercal nodules (the males migrate from nodule to nodule, fertilising females).

Skin disease (can be acute or chronic):

• acute papular onchodermatitis
• chronic onchodermatitis (sowda)

Eye disease:
Anterior segment
- Punctate keratitis – death of small groups of cells on surface of cornea
- Acute iridocyclitis – inflammation of the anterior chamber of the eye
- Sclerosing keratitis – inflammation of the cornea

Posterior segment

• Optic neuritis/atrophy – atrophy of the optic nerve
• Chorioretinopathy – fluid accumulates in the retina, causing serous detachment and vision loss

Question 15

Describe acute papular onchodermatitis.

Answer 15

It looks like an acute papular rash, but if you look under the skin, you’ll see microfilariae surrounded by an inflammatory response, characterised by a lot of eosinophils.

Question 16

Describe chronic onchodermatitis

Answer 16

With the repeated inflammation, you get damage to the elastin and collagen in the skin, so you get aged skin.

Question 17

Describe punctate keratitis.

Answer 17

The microfilariae can invade the cornea, and this is known as punctate keratitis.

Question 18

Describe sclerosing keratitis.

Answer 18

With the repeated inflammation, you can get chronic inflammation of the cornea, which leads to eventual occlusion; this is known as sclerosing keratitis.

Question 19

Describe chorioretinopathy

Answer 19

With chronic inflammation, you get damage to the retina. If the retinal pigment epithelial dies, the overlying neural cells die as well. We can then see the choroid, underneath the retina.

Once the persona loses their macula, they become blind.

Question 20

Describe optic atrophy.

Answer 20

You will also see the sheathing of the blood vessels caused by inflammation. The pale optic disc is common of optic atrophy.

Question 21

Describe the immunopathogenesis of onchocerciasis.

Answer 21

In acute disease, we get there rapid allergic reactions where microfilariae are dying.

In the acute phase we have a strong Th2 response, with production of IL-4 (to make IgE) and IL-5 (to both recruit and activate eosinophils).

With chronic inflammation, the immune response starts to shut down; the host immune system starts to become regulated. Key to this is a modified Th2 response, where we get production of IL-10, Treg cells and antibodies such as IgG4, all of which are important in immune regulation.
The parasite switches on host regulatory response in order to survive and the host has to downregulate inflammation in order to survive, so it is a complex reaction between the host and the parasite.

Question 22

How does a tick attach itself to an organism?

Answer 22

The tick stick its mouth part into the skin and from a cement that keeps it lodged on, making it hard to get off.
It sits there and sucks the blood of the organism.

Question 23

Describe the two types of ticks.

Answer 23

Hard ticks (Ixodidae):

• have a dorsal plate
• have a visible capitulum
• when filled with blood, get an enormous abdomen

Soft tick (Omithodorus):
- capitulum is not visible

Question 24

List some diseases transmitted by ticks.

Answer 24

Hard ticks:

• Tick typhus
• Viral encephalitis
• Viral fevers
• Viral haemorrhagic fevers
• Tularemia
• Tick paralysis
• Human babesiosis

Soft ticks:

• Q fever
• Relapsing fever (caused by Borrelia duttoni)

Question 25

Describe tick paralysis.

Answer 25

It is the result of progressive flaccidity due to a failure of acetylcholine liberation in the neuromuscular junction.
The tick’s toxins produce a block in the motor nerve fibers.

Question 26

Describe head lice.

Answer 26

They suck blood from the scalp and lay eggs on hair.

They are common and easily spread by close contact, sharing of combs, brushed, hats, etc.

Question 27

Describe body lice.

Answer 27

They suck blood and lay eggs on clothing.

These are uncommon and spread by bodily contact, sharing of clothing or bedding.
They transmit vector diseases such as epidemic typhus, trench fever, relapsing fever, etc.

Question 28

What is the classification of sucking lice?

Answer 28

They are one of the 2 important families of lice (that attack humans).

Question 29

Describe pthiridae.

Answer 29

They are known as crab lice, or pubic lice.

They are broad, flat live that appear crab-like. Their mid and hind legs are stout with very large claws, and their abdomens have distinct lateral lobes.

There is a single species (pthirus pubus) confined to the human pubic region.
Their bites cause irritation and the typical rash. It is spread by close bodily contact (normally sex).

Question 30

Describe how a botfly infects organisms.

Answer 30

Mid-flight, it grabs and mosquito and lays it’s eggs on it, and that mosquito goes and bites an animal. When the mosquito alights on the body, there is a change in temperature, and the tick hatches, and migrates into the skin.
It’s more common in cattle – but humans can also be infected.

Question 31

Describe the manifestation of botfly larvae in an organism (myasis).

Answer 31

You can just see the head, the rest of the body is under the skin.
It has a row of spines that it sticks into the surrounding tissue when we try to get it out, making it very hard to extract.

Eventually, if you leave it inside of you, it will drop out. However, it wiggles inside of you, which people find very uncomfortable.

If the larvae multiply too much and it is left intreated, it will result in death.

Question 32

List some medications that are used against protozoa, helminths and extoparasites.

Answer 32

PROTOZOA:

• Tinidazole – has shorter dose regimens
• Metronidazole – has more adverse reactions and you give for a week/2 week course, 2/3 a day, it’s not a very good treatment as it is not well-tolerated
• Nitazoxinaide – used to treat some protozoal infections
• Benznidazole – (treats Chagas disease) but you get nasty adverse reactions, people can’t complete treatment course
• Heavy metals (meglumine antimoniate): used to be used in the past

HELMINTHS:

• Albendazole/ mebendazole - given once in a single dose is effective in curing infection
• Praziquantel – useful for the treatment of trematodes
• Ivermectin – a single dose is effective, gets rid of or kills the parasites
• Diethylcarbamazine
• Pyrantel

ECTOPARASITES:

• Ivermectin – a single dose is effective, gets rid of or kills the parasites
• Benzyl/malathion lotions – have to repeat, the treatment is not that effective

Question 33

How can we control parasitic infections?

Answer 33

BEHAVIOURS:

• Education
• Hand washing and hygiene behaviours

ENVIRONMENTAL INTERVENTIONS:

• Spraying of residual insecticides for household vectors
• Mosquito nets for malaria (though some bugs just live in nearby palm trees)
• Improved housing
• Sewage disposal and potable water
• Drainage of swamps

POVERTY REDUCTION:
- Micro-financing, etc

Question 34

In terms of control of parasitic infections, what are the implications of the treatment regime?

Answer 34

For many parasite infections in an endemic settings, treatment must be given periodically over long periods of time because re-infections are rapid or because the treatment kills larval rather than adult stages.

For example:

• a single dose of albendazole is given to high risk groups such as schoolchildren up to every 4 months to control STH infections.
• a single dose of ivermectin is given to endemic communities (mass drug administration) every 6 or 12 months to control onchocerciasis (kills larvae, not the adults)
• a single dose of praziquantel is given to endemic communities (mass drug administration) every 6 or 12 months to control schistosomiasis (used to try and control the infection, and try to cure it in the community)